U.S. Pat. No. 5,714,316, which is incorporated herein by reference, describes the design and production of viral particles which display heterologous protein sequences on the viral particle envelope.
U.S. Pat. Nos. 4,873,089, 5,227,470 and 5,258,499, which are incorporated herein by reference, describe methods of preparing liposomes that contain proteins displayed on their surfaces in order to target the liposomes to a cell with a cellular protein on its surface that specifically binds to the protein on the surface of the liposome.
U.S. Pat. Nos. 5,837,533, 5,459,127 and Behr, J. P., et al. (1989) Proc. Natl. Acad. Sci. USA 86:6982-6986, which are each incorporated herein by reference, describe the design and production of receptor targeted cationic amphiphile/DNA complexes in which positively charged lipophilic compounds are provided with receptor ligands. The cationic amphiphilic compounds contain receptor ligand moieties which are displayed on the surface of complexes formed when the cationic amphiphile is mixed with DNA. Such teachings may also be applied to cationic lipid/DNA complexes such as those described in U.S. Pat. Nos. 5,955,365, 5,948,767, 5,945,400, 5,939,401, 5,935,936, 5,932,241, 5,925,628, 5,916,803, 5,910,488, 5,908,635, 5,891,468, 5,885,613, 5,830,430, 5,827,703, 5,783,565 and 5,767,099, which are incorporated herein by reference.
Improved particles for the delivery of compounds is described in Ser. No. 09/680,690 and PCT/US00/27618, which are incorporated herein by reference. The subject matter described therein includes the use of providing particles that comprise co-stimulatory molecule ligands in order to target cells that express the co-stimulatory molecules. The particles that comprise the co-stimulatory molecule ligands bind to and are taken up by cells that express the co-stimulatory molecules. Thus, compounds that are components of the particle are taken up by the cells.
The use of fusion proteins that comprise a portion of the HIV Vpr protein linked to biologically active non-HIV proteins is described in Ser. No. 08/167,608 filed Dec. 15, 1993 and PCT/US94/02191 filed Feb. 22, 1994, which are incorporated herein by reference. The subject matter described therein sets forth the use of such fusion proteins to deliver biologically active proteins using HIV particles, preferably non-replicating HIV particles to deliver the fusion proteins. About 2400 copies of the Vpr protein are packaged within the HIV particle. By providing fusion proteins with Vpr sequences that interact with the HIV particle, 2400 copies of the fusion protein can be packaged within an HIV-derived particle. Packaging systems are described in each of the following U.S. patents which are incorporated herein by reference: U.S. Pat. Nos. 5,932,467, 5,952,225, 5,932,467, 5,928,913, 5,919,676, 5,912,338, 5,888,767, 5,872,005, 5,866,411, 5,843,723, 5,834,256, 5,753,500, 5,739,018, 5,736,387, 5,723,287, 5,716,832, 5,710,037, 5,693,531, 5,672,510, 5,665,577, 5,622,856, 5,587,308 and 5,585,254.
The delivery of heterologous gene sequences for expression includes those delivered using particles as well as those which are free of such particles. For example, nucleic acid sequences may be included in viral-derived particles, liposomes or other complexes as well as in the form of free DNA delivered with or without co-agents. There are many well known applications, such as vaccine and gene therapy, for delivering nucleic acid molecules in expressible constructs to be taken up by cells and expressed. DNA vaccines are described in U.S. Pat. Nos. 5,593,972, 5,739,118, 5,817,637, 5,830,876, 5,962,428, 5,981,505, 5,580,859, 5,703,055, 5,676,594, and the priority applications cited therein, which are each incorporated herein by reference. In addition to the delivery protocols described in those applications, alternative methods of delivering DNA are described in U.S. Pat. Nos. 4,945,050 and 5,036,006, which are both incorporated herein by reference. Examples of attenuated live vaccines and those using recombinant vectors to deliver foreign antigens are described in U.S. Pat. Nos. 4,722,848; 5,017,487; 5,077,044; 5,110,587; 5,112,749; 5,174,993; 5,223,424; 5,225,336; 5,240,703; 5,242,829; 5,294,441; 5,294,548; 5,310,668; 5,387,744; 5,389,368; 5,424,065; 5,451,499; 5,453,364; 5,462,734; 5,470,734; and 5,482,713, which are each incorporated herein by reference.
There remains a need for improved particles for delivery of compounds to cells. There remains a need for improved expression systems for nucleic acid molecules delivered to cells.